Field of Invention
The present invention relates to use of a peptide secreted from B cells that has an inhibitory effect on the migration of T cells (including auto-reactive T cells). This has applications in the treatment and/or prophylaxis of the conditions associated with such T cells, most notably type 1 diabetes mellitus and Sjogren's syndrome.
Related Art
Pancreatic islet-reactive T cells play a central role in beta cell destruction and thus in the pathogenesis of type 1 diabetes (T1D). In evidence, T cells comprise a major part of the islet infiltrate in a T1D pancreas, and immunosuppressive drugs that target T cells preserve beta cell function. Understanding the mechanisms by which islet-reactive T cells are recruited from the blood, across inflamed endothelium, and into the pancreatic islet have been poorly examined in T1D.
This is particularly relevant because healthy humans can also have circulating islet reactive T cells that do no apparent harm. Therefore, we believe that in T1D, endogenous mechanisms that prohibit the trafficking of reactive T cells into the pancreas fail, and if such regulatory pathways could be re-established it may be possible to exclude auto-reactive T cells and preserve beta cell function. The adipocyte-derived cytokine, adiponectin, has a role to play in regulating T cell migration, but the picture is more complex than that as adiponectin's circulating levels do not seem to fluctuate in T1D.
T cells also play a central role in the pathology of the chronic inflammatory autoimmune disease primary Sjogren's syndrome (pSS). Sjogren's syndrome is characterized by loss of function of secretory glands, for example salivary or tear glands and autoantibody production. Lymphocyte infiltration of the salivary glands and formation of organised inflammatory aggregates of T and B-lymphocytes represent the histological hallmark of the disease. The formation of these aggregates, often organised in lymph node-like structures with formation of functional germinal centers, is associated with worsening disease prognosis, higher production of autoantibodies and development of extra nodal mucosa-associated lymphoid tissue (MALT) lymphoma. To date there is no approved therapy. In addition there are at present no diagnostic tools for early identification of pSS or to stratify patients that would benefit from immunosuppressive treatment. Thus, pSS is considered an orphan disease.